{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:48:12Z","timestamp":1787500092574,"version":"build-2736575974"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2019,11,20]],"date-time":"2019-11-20T00:00:00Z","timestamp":1574208000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,11,20]],"date-time":"2019-11-20T00:00:00Z","timestamp":1574208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Blood Cancer J."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Primary plasma cell leukemia (pPCL) is a highly aggressive plasma cell dyscrasia characterised by short remissions and very poor survival. Although the 17p deletion is associated with poor outcome and extramedullary disease in MM, its presence does not confer the degree of aggressiveness observed in pPCL. The comprehensive exploration of isoform expression and RNA splicing events may provide novel information about biological differences between the two diseases. Transcriptomic studies were carried out in nine newly diagnosed pPCL and ten MM samples, all of which harbored the 17p deletion. Unsupervised cluster analysis clearly distinguished pPCL from MM samples. In total 3584 genes and 20033 isoforms were found to be deregulated between pPCL and MM. There were 2727 significantly deregulated isoforms of non-differentially expressed genes. Strangely enough, significant differences were observed in the expression of spliceosomal machinery components between pPCL and MM, in respect of the gene, isoform and the alternative splicing events expression. In summary, transcriptome analysis revealed significant differences in the relative abundance of isoforms between pPCL and MM, even when they both had the 17p deletion. The mRNA processing pathway including RNA splicing machinery emerged as one of the most remarkable mechanisms underlying the biological differences between the two entities.<\/jats:p>","DOI":"10.1038\/s41408-019-0253-1","type":"journal-article","created":{"date-parts":[[2019,11,20]],"date-time":"2019-11-20T09:03:23Z","timestamp":1574240603000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Transcriptome analysis reveals significant differences between primary plasma cell leukemia and multiple myeloma even when sharing a similar genetic background"],"prefix":"10.1038","volume":"9","author":[{"given":"Elizabeta A.","family":"Rojas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4577-8599","authenticated-orcid":false,"given":"Luis A.","family":"Corchete","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Victoria","family":"Mateos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4120-2787","authenticated-orcid":false,"given":"Ram\u00f3n","family":"Garc\u00eda-Sanz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irena","family":"Misiewicz-Krzeminska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma C.","family":"Guti\u00e9rrez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,20]]},"reference":[{"key":"253_CR1","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.blre.2011.01.005","volume":"25","author":"F Albarracin","year":"2011","unstructured":"Albarracin, F., Fonseca, R. Plasma cell leukemia. Blood Rev. 25, 107\u2013112 (2011).","journal-title":"Blood Rev."},{"key":"253_CR2","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1038\/leu.2012.336","volume":"27","author":"C Fern\u00e1ndez de Larrea","year":"2013","unstructured":"Fern\u00e1ndez de Larrea, C. et al. Plasma cell leukemia: consensus statement on diagnostic requirements, response criteria and treatment recommendations by the International Myeloma Working Group. Leukemia 27, 780\u2013791 (2013).","journal-title":"Leukemia"},{"key":"253_CR3","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1001\/archinte.133.5.813","volume":"133","author":"RA Kyle","year":"1974","unstructured":"Kyle, R. A., Maldonado, J. E., Bayrd, E. D. Plasma cell leukemia. Report on 17 cases. Arch. Intern. Med. 133, 813\u2013818 (1974).","journal-title":"Arch. Intern. Med."},{"key":"253_CR4","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1016\/0002-9343(87)90942-9","volume":"83","author":"P Noel","year":"1987","unstructured":"Noel, P., Kyle, R. A. Plasma cell leukemia: an evaluation of response to therapy. Am. J. Med. 83, 1062\u20131068 (1987).","journal-title":"Am. J. Med."},{"key":"253_CR5","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1046\/j.1365-2141.2003.04355.x","volume":"121","author":"International Myeloma Working Group.","year":"2003","unstructured":"International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br. J. Haematol. 121, 749\u2013757 (2003).","journal-title":"Br. J. Haematol."},{"key":"253_CR6","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1182\/blood-2014-03-565051","volume":"124","author":"WI Gonsalves","year":"2014","unstructured":"Gonsalves, W. I. et al. Trends in survival of patients with primary plasma cell leukemia: a population-based analysis. Blood 124, 907\u2013912 (2014).","journal-title":"Blood"},{"key":"253_CR7","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1080\/17474086.2016.1244002","volume":"9","author":"A Neri","year":"2016","unstructured":"Neri, A. et al. Primary plasma cell leukemia 2.0: advances in biology and clinical management. Expert Rev. Hematol. 9, 1063\u20131073 (2016).","journal-title":"Expert Rev. Hematol."},{"key":"253_CR8","doi-asserted-by":"publisher","first-page":"1538","DOI":"10.1080\/10428194.2016.1250263","volume":"58","author":"R Mina","year":"2017","unstructured":"Mina, R., D\u2019Agostino, M., Cerrato, C., Gay, F., Palumbo, A. Plasma cell leukemia: update on biology and therapy. Leuk. Lymphoma 58, 1538\u20131547 (2017).","journal-title":"Leuk. Lymphoma"},{"key":"253_CR9","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-018-0140-1","volume":"8","author":"P Ravi","year":"2018","unstructured":"Ravi, P. et al. Revised diagnostic criteria for plasma cell leukemia: results of a Mayo Clinic study with comparison of outcomes to multiple myeloma. Blood Cancer J. 8, 116 (2018).","journal-title":"Blood Cancer J."},{"key":"253_CR10","doi-asserted-by":"publisher","first-page":"17514","DOI":"10.3390\/ijms160817514","volume":"16","author":"V Simeon","year":"2015","unstructured":"Simeon, V. et al. Molecular classification and pharmacogenetics of primary plasma cell leukemia: an initial approach toward precision medicine. Int. J. Mol. Sci. 16, 17514\u201317534 (2015).","journal-title":"Int. J. Mol. Sci."},{"key":"253_CR11","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1038\/leu.2008.4","volume":"22","author":"RE Tiedemann","year":"2008","unstructured":"Tiedemann, R. E. et al. Genetic aberrations and survival in plasma cell leukemia. Leukemia 22, 1044\u20131052 (2008).","journal-title":"Leukemia"},{"key":"253_CR12","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1038\/sj.leu.2402116","volume":"15","author":"NC Guti\u00e9rrez","year":"2001","unstructured":"Guti\u00e9rrez, N. C. et al. Differences in genetic changes between multiple myeloma and plasma cell leukemia demonstrated by comparative genomic hybridization. Leukemia 15, 840\u2013845 (2001).","journal-title":"Leukemia"},{"key":"253_CR13","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1182\/blood.V97.3.822","volume":"97","author":"H Avet-Loiseau","year":"2001","unstructured":"Avet-Loiseau, H. et al. Cytogenetic, interphase, and multicolor fluorescence in situ hybridization analyses in primary plasma cell leukemia: a study of 40 patients at diagnosis, on behalf of the Intergroupe Francophone du My\u00e9lome and the Groupe Fran\u00e7ais de Cytog\u00e9n\u00e9tique H\u00e9matologique. Blood 97, 822\u2013825 (2001).","journal-title":"Blood"},{"key":"253_CR14","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1002\/ajh.23339","volume":"88","author":"L Mosca","year":"2013","unstructured":"Mosca, L. et al. Genome-wide analysis of primary plasma cell leukemia identifies recurrent imbalances associated with changes in transcriptional profiles. Am. J. Hematol. 88, 16\u201323 (2013).","journal-title":"Am. J. Hematol."},{"key":"253_CR15","doi-asserted-by":"publisher","first-page":"17543","DOI":"10.18632\/oncotarget.4028","volume":"6","author":"I Cifola","year":"2015","unstructured":"Cifola, I. et al. Whole-exome sequencing of primary plasma cell leukemia discloses heterogeneous mutational patterns. Oncotarget 6, 17543\u201317558 (2015).","journal-title":"Oncotarget"},{"key":"253_CR16","doi-asserted-by":"publisher","first-page":"2398","DOI":"10.1038\/leu.2012.107","volume":"26","author":"SZ Usmani","year":"2012","unstructured":"Usmani, S. Z. et al. Primary plasma cell leukemia: clinical and laboratory presentation, gene-expression profiling and clinical outcome with Total Therapy protocols. Leukemia 26, 2398\u20132405 (2012).","journal-title":"Leukemia"},{"key":"253_CR17","doi-asserted-by":"publisher","first-page":"3247","DOI":"10.1158\/1078-0432.CCR-12-3461","volume":"19","author":"K Todoerti","year":"2013","unstructured":"Todoerti, K. et al. Transcriptional characterization of a prospective series of primary plasma cell leukemia revealed signatures associated with tumor progression and poorer outcome. Clin. Cancer Res. 19, 3247\u20133258 (2013).","journal-title":"Clin. Cancer Res."},{"key":"253_CR18","doi-asserted-by":"publisher","first-page":"3130","DOI":"10.1158\/1078-0432.CCR-12-2043","volume":"19","author":"M Lionetti","year":"2013","unstructured":"Lionetti, M. et al. Biological and clinical relevance of miRNA expression signatures in primary plasma cell leukemia. Clin. Cancer Res. 19, 3130\u20133142 (2013).","journal-title":"Clin. Cancer Res."},{"key":"253_CR19","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.leukres.2018.09.007","volume":"73","author":"K Todoerti","year":"2018","unstructured":"Todoerti, K. et al. Global methylation patterns in primary plasma cell leukemia. Leuk. Res. 73, 95\u2013102 (2018).","journal-title":"Leuk. Res."},{"key":"253_CR20","doi-asserted-by":"publisher","first-page":"2461","DOI":"10.1038\/sj.onc.1208447","volume":"24","author":"M Mattioli","year":"2005","unstructured":"Mattioli, M. et al. Gene expression profiling of plasma cell dyscrasias reveals molecular patterns associated with distinct IGH translocations in multiple myeloma. Oncogene 24, 2461\u20132473 (2005).","journal-title":"Oncogene"},{"key":"253_CR21","doi-asserted-by":"publisher","first-page":"1692","DOI":"10.1158\/1078-0432.CCR-10-1066","volume":"17","author":"L L\u00f3pez-Corral","year":"2011","unstructured":"L\u00f3pez-Corral, L. et al. The progression from MGUS to smoldering myeloma and eventually to multiple myeloma involves a clonal expansion of genetically abnormal plasma cells. Clin. Cancer Res. 17, 1692\u20131700 (2011).","journal-title":"Clin. Cancer Res."},{"key":"253_CR22","doi-asserted-by":"publisher","first-page":"2223","DOI":"10.1200\/JCO.2010.32.0838","volume":"29","author":"D Gonzalez","year":"2011","unstructured":"Gonzalez, D. et al. Mutational status of the TP53 gene as a predictor of response and survival in patients with chronic lymphocytic leukemia: results from the LRF CLL4 trial. J. Clin. Oncol. 29, 2223\u20132229 (2011).","journal-title":"J. Clin. Oncol."},{"key":"253_CR23","doi-asserted-by":"publisher","first-page":"W130","DOI":"10.1093\/nar\/gkx356","volume":"45","author":"J Wang","year":"2017","unstructured":"Wang, J., Vasaikar, S., Shi, Z., Greer, M., Zhang, B. WebGestalt 2017: a more comprehensive, powerful, flexible and interactive gene set enrichment analysis toolkit. Nucleic Acids Res. 45, W130\u2013W137 (2017).","journal-title":"Nucleic Acids Res."},{"key":"253_CR24","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1093\/bioinformatics\/btp124","volume":"25","author":"F Piva","year":"2009","unstructured":"Piva, F., Giulietti, M., Nocchi, L., Principato, G. SpliceAid: a database of experimental RNA target motifs bound by splicing proteins in humans. Bioinf. Oxf. Engl. 25, 1211\u20131213 (2009).","journal-title":"Bioinf. Oxf. Engl."},{"key":"253_CR25","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1038\/nsmb.2207","volume":"19","author":"O Anczuk\u00f3w","year":"2012","unstructured":"Anczuk\u00f3w, O. et al. The splicing factor SRSF1 regulates apoptosis and proliferation to promote mammary epithelial cell transformation. Nat. Struct. Mol. Biol. 19, 220\u2013228 (2012).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"253_CR26","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.molcel.2015.09.005","volume":"60","author":"O Anczuk\u00f3w","year":"2015","unstructured":"Anczuk\u00f3w, O. et al. SRSF1-regulated alternative splicing in breast cancer. Mol. Cell 60, 105\u2013117 (2015).","journal-title":"Mol. Cell"},{"key":"253_CR27","doi-asserted-by":"publisher","first-page":"1920","DOI":"10.1158\/1541-7786.MCR-18-1291","volume":"17","author":"JT DeLigio","year":"2019","unstructured":"DeLigio, J. T. et al. Serine\/Arginine-Rich Splicing Factor 3 modulates the alternative splicing of cytoplasmic polyadenylation element binding protein 2. Mol. Cancer Res. 17, 1920\u20131930 (2019).","journal-title":"Mol. Cancer Res."},{"key":"253_CR28","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1158\/1541-7786.MCR-14-0131","volume":"12","author":"S Das","year":"2014","unstructured":"Das, S., Krainer, A. R. Emerging functions of SRSF1, splicing factor and oncoprotein, in RNA metabolism and cancer. Mol. Cancer Res. 12, 1195\u20131204 (2014).","journal-title":"Mol. Cancer Res."},{"key":"253_CR29","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/nsmb1209","volume":"14","author":"R Karni","year":"2007","unstructured":"Karni, R. et al. The gene encoding the splicing factor SF2\/ASF is a proto-oncogene. Nat. Struct. Mol. Biol. 14, 185\u2013193 (2007).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"253_CR30","doi-asserted-by":"publisher","first-page":"1854","DOI":"10.1093\/nar\/gkv1500","volume":"44","author":"M Ajiro","year":"2016","unstructured":"Ajiro, M., Jia, R., Yang, Y., Zhu, J., Zheng, Z.-M. A genome landscape of SRSF3-regulated splicing events and gene expression in human osteosarcoma U2OS cells. Nucleic Acids Res. 44, 1854\u20131870 (2016).","journal-title":"Nucleic Acids Res."},{"key":"253_CR31","doi-asserted-by":"publisher","DOI":"10.1186\/gm437","volume":"5","author":"Z Zhang","year":"2013","unstructured":"Zhang, Z., Pal, S., Bi, Y., Tchou, J., Davuluri, R. V. Isoform level expression profiles provide better cancer signatures than gene level expression profiles. Genome Med. 5, 33 (2013).","journal-title":"Genome Med."},{"key":"253_CR32","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku121","volume":"42","author":"S Pal","year":"2014","unstructured":"Pal, S. et al. Isoform-level gene signature improves prognostic stratification and accurately classifies glioblastoma subtypes. Nucleic Acids Res. 42, e64 (2014).","journal-title":"Nucleic Acids Res."},{"key":"253_CR33","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/S0968-0004(00)01549-8","volume":"25","author":"BJ Blencowe","year":"2000","unstructured":"Blencowe, B. J. Exonic splicing enhancers: mechanism of action, diversity and role in human genetic diseases. Trends Biochem. Sci. 25, 106\u2013110 (2000).","journal-title":"Trends Biochem. Sci."},{"key":"253_CR34","doi-asserted-by":"publisher","first-page":"5053","DOI":"10.1093\/nar\/gki810","volume":"33","author":"J Wang","year":"2005","unstructured":"Wang, J., Smith, P. J., Krainer, A. R., Zhang, M. Q. Distribution of SR protein exonic splicing enhancer motifs in human protein-coding genes. Nucleic Acids Res. 33, 5053\u20135062 (2005).","journal-title":"Nucleic Acids Res."},{"key":"253_CR35","doi-asserted-by":"publisher","unstructured":"van Andel H., Kocemba K. A., Spaargaren M., Pals S. T. Aberrant Wnt signaling in multiple myeloma: molecular mechanisms and targeting options. Leukemia (2019). https:\/\/doi.org\/10.1038\/s41375-019-0404-1.","DOI":"10.1038\/s41375-019-0404-1"},{"key":"253_CR36","doi-asserted-by":"publisher","first-page":"2376","DOI":"10.1182\/blood-2012-05-408682","volume":"120","author":"NWCJ van de Donk","year":"2012","unstructured":"van de Donk, N. W. C. J., Lokhorst, H. M., Anderson, K. C. & Richardson, P. G. How I treat plasma cell leukemia. Blood 120, 2376\u20132389 (2012).","journal-title":"Blood"},{"key":"253_CR37","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-018-0196-9","volume":"51","author":"M Jin","year":"2019","unstructured":"Jin, M. Unique roles of tryptophanyl-tRNA synthetase in immune control and its therapeutic implications. Exp. Mol. Med. 51, 1 (2019).","journal-title":"Exp. Mol. Med."},{"key":"253_CR38","doi-asserted-by":"publisher","unstructured":"Lee H.-C. et al. Released tryptophanyl-tRNA synthetase stimulates innate immune responses against viral infection. J. Virol. 93, (2019). https:\/\/doi.org\/10.1128\/JVI.01291-18.","DOI":"10.1128\/JVI.01291-18"},{"key":"253_CR39","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1128\/IAI.02765-14","volume":"83","author":"CN Ellis","year":"2015","unstructured":"Ellis, C. N. et al. Comparative proteomic analysis reveals activation of mucosal innate immune signaling pathways during cholera. Infect. Immun. 83, 1089\u20131103 (2015).","journal-title":"Infect. Immun."},{"key":"253_CR40","doi-asserted-by":"publisher","first-page":"6669","DOI":"10.1073\/pnas.0401771101","volume":"101","author":"S Wieland","year":"2004","unstructured":"Wieland, S., Thimme, R., Purcell, R. H., Chisari, F. V. Genomic analysis of the host response to hepatitis B virus infection. Proc. Natl Acad. Sci. USA 101, 6669\u20136674 (2004).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"253_CR41","doi-asserted-by":"publisher","first-page":"14470","DOI":"10.1073\/pnas.95.24.14470","volume":"95","author":"H Zhu","year":"1998","unstructured":"Zhu, H., Cong, J. P., Mamtora, G., Gingeras, T., Shenk, T. Cellular gene expression altered by human cytomegalovirus: global monitoring with oligonucleotide arrays. Proc. Natl Acad. Sci. USA 95, 14470\u201314475 (1998).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"253_CR42","doi-asserted-by":"publisher","first-page":"3221","DOI":"10.1073\/pnas.1601773113","volume":"113","author":"N Lee","year":"2016","unstructured":"Lee, N., Yario, T. A., Gao, J. S., Steitz, J. A. EBV noncoding RNA EBER2 interacts with host RNA-binding proteins to regulate viral gene expression. Proc. Natl Acad. Sci. USA 113, 3221\u20133226 (2016).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"253_CR43","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1080\/15476286.2018.1518854","volume":"15","author":"AV Nanni","year":"2018","unstructured":"Nanni, A. V., Lee, N. Identification of host RNAs that interact with EBV noncoding RNA EBER2. RNA Biol. 15, 1181\u20131191 (2018).","journal-title":"RNA Biol."},{"key":"253_CR44","doi-asserted-by":"publisher","first-page":"286","DOI":"10.3389\/fimmu.2018.00286","volume":"9","author":"P Xue","year":"2018","unstructured":"Xue, P., Fu, J., Zhou, Y. The aryl hydrocarbon receptor and tumor immunity. Front. Immunol. 9, 286 (2018).","journal-title":"Front. Immunol."},{"key":"253_CR45","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s13000-018-0740-x","volume":"13","author":"Z-Y Pan","year":"2018","unstructured":"Pan, Z.-Y. et al. Activation and overexpression of the aryl hydrocarbon receptor contribute to cutaneous squamous cell carcinomas: an immunohistochemical study. Diagn. Pathol. 13, 59 (2018).","journal-title":"Diagn. Pathol."},{"key":"253_CR46","doi-asserted-by":"publisher","first-page":"4651","DOI":"10.1158\/0008-5472.CAN-15-2011","volume":"75","author":"NC D\u2019Amato","year":"2015","unstructured":"D\u2019Amato, N. C. et al. A TDO2-AhR signaling axis facilitates anoikis resistance and metastasis in triple-negative breast cancer. Cancer Res. 75, 4651\u20134664 (2015).","journal-title":"Cancer Res."},{"key":"253_CR47","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/S0006-291X(02)02793-6","volume":"300","author":"T Hayashibara","year":"2003","unstructured":"Hayashibara, T. et al. Possible involvement of aryl hydrocarbon receptor (AhR) in adult T-cell leukemia (ATL) leukemogenesis: constitutive activation of AhR in ATL. Biochem. Biophys. Res. Commun. 300, 128\u2013134 (2003).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"253_CR48","doi-asserted-by":"publisher","first-page":"6059","DOI":"10.1038\/sj.onc.1205633","volume":"21","author":"A Koliopanos","year":"2002","unstructured":"Koliopanos, A. et al. Increased arylhydrocarbon receptor expression offers a potential therapeutic target for pancreatic cancer. Oncogene 21, 6059\u20136070 (2002).","journal-title":"Oncogene"},{"key":"253_CR49","doi-asserted-by":"publisher","first-page":"2593","DOI":"10.1038\/onc.2009.104","volume":"28","author":"D Gramatzki","year":"2009","unstructured":"Gramatzki, D. et al. Aryl hydrocarbon receptor inhibition downregulates the TGF-beta\/Smad pathway in human glioblastoma cells. Oncogene 28, 2593\u20132605 (2009).","journal-title":"Oncogene"},{"key":"253_CR50","doi-asserted-by":"publisher","first-page":"4682","DOI":"10.1172\/JCI70712","volume":"128","author":"A Bianchi-Smiraglia","year":"2018","unstructured":"Bianchi-Smiraglia, A. et al. Inhibition of the aryl hydrocarbon receptor\/polyamine biosynthesis axis suppresses multiple myeloma. J. Clin. Invest. 128, 4682\u20134696 (2018).","journal-title":"J. Clin. Invest."},{"key":"253_CR51","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.advms.2018.08.018","volume":"64","author":"J Szefel","year":"2018","unstructured":"Szefel, J., Danielak, A., Kruszewski, W. J. Metabolic pathways of L-arginine and therapeutic consequences in tumors. Adv. Med. Sci. 64, 104\u2013110 (2018).","journal-title":"Adv. Med. Sci."},{"key":"253_CR52","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.1182\/blood-2006-06-031856","volume":"109","author":"PC Rodriguez","year":"2007","unstructured":"Rodriguez, P. C., Quiceno, D. G., Ochoa, A. C. L-arginine availability regulates T-lymphocyte cell-cycle progression. Blood 109, 1568\u20131573 (2007).","journal-title":"Blood"},{"key":"253_CR53","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1126\/science.1244851","volume":"343","author":"J Kr\u00f6nke","year":"2014","unstructured":"Kr\u00f6nke, J. et al. Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science 343, 301\u2013305 (2014).","journal-title":"Science"},{"key":"253_CR54","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1182\/blood-2014-02-557819","volume":"124","author":"YX Zhu","year":"2014","unstructured":"Zhu, Y. X. et al. Identification of cereblon-binding proteins and relationship with response and survival after IMiDs in multiple myeloma. Blood 124, 536\u2013545 (2014).","journal-title":"Blood"},{"key":"253_CR55","doi-asserted-by":"publisher","first-page":"7111","DOI":"10.1128\/MCB.14.11.7111","volume":"14","author":"K Hahm","year":"1994","unstructured":"Hahm, K. et al. The lymphoid transcription factor LyF-1 is encoded by specific, alternatively spliced mRNAs derived from the Ikaros gene. Mol. Cell Biol. 14, 7111\u20137123 (1994).","journal-title":"Mol. Cell Biol."},{"key":"253_CR56","doi-asserted-by":"publisher","first-page":"5358","DOI":"10.1002\/j.1460-2075.1996.tb00920.x","volume":"15","author":"L Sun","year":"1996","unstructured":"Sun, L., Liu, A., Georgopoulos, K. Zinc finger-mediated protein interactions modulate Ikaros activity, a molecular control of lymphocyte development. EMBO J. 15, 5358\u20135369 (1996).","journal-title":"EMBO J."},{"key":"253_CR57","doi-asserted-by":"publisher","first-page":"2166","DOI":"10.1182\/blood-2018-05-850727","volume":"132","author":"PL Fedele","year":"2018","unstructured":"Fedele, P. L. et al. IMiDs prime myeloma cells for daratumumab-mediated cytotoxicity through loss of Ikaros and Aiolos. Blood 132, 2166\u20132178 (2018).","journal-title":"Blood"},{"key":"253_CR58","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1073\/pnas.96.2.680","volume":"96","author":"L Sun","year":"1999","unstructured":"Sun, L. et al. Expression of dominant-negative and mutant isoforms of the antileukemic transcription factor Ikaros in infant acute lymphoblastic leukemia. Proc. Natl Acad. Sci. USA 96, 680\u2013685 (1999).","journal-title":"Proc. Natl Acad. Sci. USA"}],"container-title":["Blood Cancer Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41408-019-0253-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41408-019-0253-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41408-019-0253-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T11:15:05Z","timestamp":1671189305000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41408-019-0253-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,20]]},"references-count":58,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["253"],"URL":"https:\/\/doi.org\/10.1038\/s41408-019-0253-1","relation":{},"ISSN":["2044-5385"],"issn-type":[{"value":"2044-5385","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,20]]},"assertion":[{"value":"4 June 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 October 2019","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 October 2019","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 November 2019","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Dr. Mateos reports personal fees from Janssen, Celgene, Amgen, Takeda, Pharmamar, GSK, AbbVie and Adaptive, outside the submitted work. Dr. Garcia-Sanz reports personal fees from Amgen, Janssen, Takeda and Pfizer, outside the submitted work. Dr. Guti\u00e9rrez reports honoraria from Janssen outside the submitted work. The other authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This study was partially supported by the Instituto de Salud Carlos III cofinanced by the European Union FEDER funds (PI13\/00111 and PI16\/01074), Gerencia Regional de Salud, Junta de Castilla y Le\u00f3n (BIO\/SA57\/13) and the Asociaci\u00f3n Espa\u00f1ola Contra el C\u00e1ncer (AECC, GCB120981SAN). E.A.R.R. was supported by the Consejer\u00eda de Educaci\u00f3n de Castilla y Le\u00f3n and FEDER funds. I.M.K. and L.A.C. were supported by the Sociedad Espa\u00f1ola de Hematolog\u00eda y Hemoterapia.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}}],"article-number":"90"}}